Genetics and psychiatry

The previous year marked the celebration of the 50th anniversary of the description, in 1953, of the
double helix of the DNA structure by Watson and Crick. the same period of time, as 11Vatson and Crick's
breakthrough, chlorpromazine was synthesised in Couvoisier's laboratory and used in clinical practice by the
psychiatrists Delay and Deniker. The use of chlorpromazine by changing dramatically the picture of mental
illness is considered as the third revolution in psychiatry, after the delivery of patients from the chains by Pinel
(1745-1826) and the theory of Freud (1856-1939).
The term genetcs l genetc was already used by Bateson in 1902, while the differentiation between the
concept of genotype and phenotype was provided in 1909 by the Danish botanist Johanssen, who was the first
to introduce the term gen~. The question about the role of heredity in the etiology of psychiatric disorders,
mainly the major ones - schizophrenia and aftective disorder - has occupied medical thinking since the 1,9th
century (the method for studying twins was proposed by Galton in 1875). Based empirical observations,
even at the time of Kraepelin, it was reported that these disorders were frequently presented in the families of
patients.
Since 1960, the systematic investigation of the contribution of genetic factors in the pathogenesis of
psychiatric disorders was significantly advanced, grace to the utilization of more strict diagnostic criteria, the
use of carefully selected control groups and mainly the application of molecular biology techniques in
psychiatric genetics.
Family studies have demonstrated the familial component of major psychiatric disorders, as welf as of the
disorders of the schizophrenic and affective spectrums and have verified the previous empirical observations
that the morbidity risk is significantly higher among the relatives of patients in comparison with the relatives of
normal controls:
Twin studies have shown that familiality of psychiatric dsorders is mainly due to the influence of heredity,
by demonstrating that the concordance for these disorders was higher in monozygotic () twins, who share
identical genetic material, in comparison to dizygotic (DZ) twins, who share only half of their genes; the
findings were consistent either the twins ( and DZ) had been reared together or apart. However, the fact
that the concordance rate in twins is less than 100%, as would have been the case if the disorders were
only due to genetic factors, supports also the hypothesis that environmental influences are also implicated in
the manifestation of the diseases. Finally, adoption studies have verified the hypothesis of genetic contribution,
by demonstrating that psychiatric disorders are more frequently expressed among the biological rather than
the adoptive relatives of patients.
The results of the association and linkage studies of major psychiatric disorders with various genetic
markers and candidate genes in different chromosomal regions, as well as those regarding whole genome
scans were positive for lot of the respective studies, while other studies presented negative conclusions or
were not able to verify previous findings. This is believed to be related to problems with the exact definition of
the phenotype, due to the multiformity of its clinical expression, as well as with the genetic and clinical
heterogeneity of mental illness. diseases with classical mendelian transmission the genotype usually
corresponds directly to the phenotype, while this is not the case for diseases such as the major psychiatric
disorders, with multigenic-multifactorial mode of transmission. It seems that in this kind of disorders a number
of genes interact with environmental factors and contribute to the manifestation of the disease. What is
inherited in the end, is not the certainty that someone will develop the disorder, but susceptibility which may
be manifested through subclinical characteristics, and which is translated into disease if it exceeds threshold
during the person's
life-time.
n our days, psychiatry, based the dramatic progress in the field of neurosciences and the completion
of the mapping of the human genome as well as the progress in pharmacogenetics and, particularly, its
most promising area of pharmacogenomics, seems to be entering its fourth revolution.

George . Papadmtrou
Assoc. Professor of Psychatry Universty of Athens

REFERENCES

1. Rutter , Plomin R. Opportunities for psychiatry from genetic findings. -J Psychatry 1997, 171: 209-219.
2. Papadimitriou GN, Mendlewicz J (eds). Genetics of Mental Disorders. Part : Clinical Issues. Bailliere-Tindall,
London, 1996.
3. Papadimitriou GN, Dikeos DG, Stefanis CN. Psychiatric genetic research in Greece. PsychiatrGenet 1999,
9:115-121.
4. Baron . Manic-depression genes and the new millennium: poised for discovery. Psychatry2002, :342-
358.
5. Papadimitriou GN, Dikeos DG. w does recent knowledge n the heredity of schizophrenia affect genetic
counseling? Curr Psychiatry Rep2003, 5: 239-240.